FDA approves Keytruda combo for first-line lung cancer treatment

Patients in the United States with advanced nonsquamous non-small cell lung cancer (NSCLC)—regardless of PD-L1 expression—can now receive the immunotherapy Keytruda® (pembrolizumab, Merck, also known as MSD outside the U.S. and Canada) as a first-line treatment in combination with chemotherapy.

The FDA’s recent accelerated approval was based on the phase I/II Keynote-021 trial, in which a cohort of 123 patients with metastatic, non-squamous non-small cell lung cancer (NSCLC) were treated with either chemotherapy alone (a pemetrexed and carboplatin regimen) or along with Keytruda, a checkpoint inhibitor that prevents the activation of the PD-1 receptor via the PD-L1 protein. Blocking this interaction can enable immune cells to sustain their activity against tumors.

Of the 60 patients who received the combination of immunotherapy and chemotherapy, 55% had their tumors shrink by at least 30%. Of the 63 patients who received chemotherapy alone, only 29% responded. Furthermore, progression free survival (PFS) improved in patients who also received immunotherapy: 93% of these combination-treated patients had no evidence of progression at 6 months post-treatment compared to 81% of the chemotherapy treated group, while the median PFS for each group was 13 months versus 8.9 months, respectively.

However, there was no improvement observed with regard to overall survival, as this study was too small and was not designed to show this. A larger study is currently under way that is designed to determine if there is an overall survival difference.

While Keytruda is already approved in the US as a standalone first-line therapy for advanced NSCLC patients whose tumors express high levels of PD-L1, this latest approval now extends this important immunotherapy option to more patients with the lung cancer, even those whose tumors lack PD-L1.

This most recent Keytruda approval, unusual as it is based on data from a relatively small clinical trial, also highlights the merits of the FDA’s commitment to help ensure that the most promising therapies are made available to patients as soon as is reasonably possible, especially with high priority patient populations such as lung cancer.

Keytruda currently is also approved for first-line treatment of advanced melanoma as well as for second-line treatment of head and neck cancer patients whose tumors have not responded to standard-of-care chemotherapy.